Scientific and Medical Aspects of Human Reproductive Cloning (2002) / Chapter Skim
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3. Animal Cloning
3. Animal Cloning
Pages 39-60
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From page 39... ...
Similar attempts have been made in rhesus macaques, but the only success has been in experiments with nuclei from preimplantation embryos rather than postembryonic cells [30; 31~. In addition, reproductive cloning efforts in rabbits, rats, cats, dogs, and horses are ongoing [32~.
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From page 40... ...
In humans, late gestational fetal loss causes increased maternal morbidity and mortality. Cloning studies in animals have shown that a high proportion of pregnancies involving cloned fetuses have abnormalities, including abnormal placentation, pregnancy toxemia, and hydroallantois excessive fluid accumulation in the uterus often associated with fetal abnormality [14; 33; 43; 100; 101; 115~.
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From page 41... ...
cannot be diagnosed or prevented with current technology, such as prenatal screening with ultrasonography. Many of the defects seen in cloned cattle and sheep (for example, high birth weight, abnormal placentation, fluid accumulation associated with maternal and fetal distress, and cardiovascular abnormalities)
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From page 42... ...
In conclusion, if results from animal reproductive cloning studies are extrapolated to humans, they suggest that reproductive cloning of humans could carry a very high risk to the health of both fetus or infant and mother and lead to associated psychological risks for the parents as a consequence of late spontaneous abortions or the birth of a stillborn child or a child with severe health problems. Moreover, if the cloned human fetus or placenta grew abnormally large, this could cause problems before a cesarean section would be an option, particularly if multiple embryos are placed in the uterus, which is the procedure in most IVF clinics in the United States.
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From page 43... ...
When researchers place animal somatic cell nuclei into enucleated eggs, they expect to "coerce" the adult cell nucleus into responding to egg cytoplasm as though it were the nucleus of a zygote. The nucleus should switch off many of the genes that were active in the adult cells and "restart" the genes needed to support the growth of embryonic tissues.
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From page 44... ...
In the embryo and resulting offspring, the mark controls whether the gene is expressed. The best characterized of these marks is a methyl chemical group, which is added to some segments of the DNA in regions near the imprinted genes that are termed imprint control regions.
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From page 45... ...
Similar effects seen in some animal reproductive cloning experiments lead scientists to suspect a common cause. Although a direct link has not yet been demonstrated in most cases, mice cloned using ES cells as nucleus donors show widespread, unpredictable and aberrant regulation of their imprinted genes, as well as developmental abnormalities [75~.
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From page 46... ...
This process might work properly only if the cellular machinery is faced with two distinct sets of DNA from a sperm and an egg [70~. Nuclear transplantation, however, presents the egg cytoplasm with two sets of DNA from a single somatic cell.
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From page 47... ...
When the SCNT procedure is used, the incoming nuclear DNA will encounter a foreign set of egg-derived mitochondrial DNA. That has the potential to cause problems because, for example, there are natural variants of both nuclear and mitochondrial genes, and some pair combinations work less efficiently than others [108-110~.
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From page 48... ...
Any shortening of telomeres in cloned sheep appears to be minor and can be minimized by judicious choice of the cell type used as a nucleus donor [116~. No sign of telomere shortening or aging was seen in mice cloned serially for six generations [25]
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From page 49... ...
Studies often differ in species used, method of nuclear transplantation (fusion or injection, and single transfer or serial transfer) , method of egg activation, expertise of the investigators, and condition of cells used as nucleus donor (for example, different cell type, cell cycle stage, and time of growth in culture before nuclear transplantation)
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From page 50... ...
Another early approach to improve reproductive cloning efficiency involved delaying the activation of the egg after nuclear transplantation; theoretically, this should allow more time for the regulatory proteins to be stripped off the incoming DNA and for cytoplasmic proteins to bind to the DNA [23~. Again, this strategy has not led to a solution to low cloning efficiencies.
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From page 51... ...
Reproductive cloning with nuclear transplantation from adult cells has not yet been performed successfully in nonhuman primates, so no data on the efficiency or safety of the procedure in primates are available. Such data might be helpful in assessing the possible results of a human reproductive cloning attempt, given the close evolutionary relationship and reproductive similarities of humans and nonhuman primates.
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From page 52... ...
CAMPBELL KH, COLMAN A, SCHNIEKE AK, KIND AJ. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells.
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From page 53... ...
WELLS DN, MISICA PM, TERVIT HR, VIVANCO WH. Adult somatic cell nuclear transfer is used to preserve the last surviving cow of the Enderby Island cattle breed.
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From page 54... ...
clones following nuclear transfer with transfected and nontransfected fetal fibroblasts and in vitro-matured oocytes. Biol Reprod 2001 Mar, 64~3~:849-56.
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From page 55... ...
STICK SL, STRELCHENKO NS, KEEFER CL, MATTHEWS L Pluripotent bovine embryonic cell lines direct embryonic development following nuclear transfer.
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From page 56... ...
HALL V, TROUNSON AO. Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulosa cell nuclei.
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From page 57... ...
Proc Natl Acad Sci U S A 1995 Nov 07, 92~23~:10782-6.
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From page 58... ...
EVANS MJ, GURER C, LOIKE JD, WILMUT I, SCHNIEKE AK, SCHON EA. Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep.
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From page 59... ...
YANG X Telomerase activity in early bovine embryos derived from parthenogenetic activation and nuclear transfer.
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From page 60... ...
Proc Natl Acad Sci U S A 1996 Nov 12, 93~23~:13010-3.
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